US2013122022A1PendingUtilityA1

Sequence of stro-1 antibody variable region

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Assignee: TOROK-STORB BEVERLYPriority: Jan 30, 2006Filed: Dec 19, 2011Published: May 16, 2013
Est. expiryJan 30, 2026(expired)· nominal 20-yr term from priority
A61K 51/1027C07K 16/28G01N 2333/705C07K 2317/56A61P 35/00
48
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Claims

Abstract

The amino acid sequence of the heavy chain polypeptide and the light chain polypeptide of the STRO-1 antibody is disclosed. Also disclosed are methods for detecting and isolating cells expressing the STRO-1 cell surface protein.

Claims

exact text as granted — not AI-modified
1 . A recombinant antibody comprising a heavy chain polypeptide, wherein the heavy chain polypeptide comprises the amino acid sequence of SEQ ID NO:1 (EVQLQQSGPD LVKPGASVKI SCKASGYSFT GYYMHWVKQS HGKSLEWIGR VNPNNGGTSY NQKFKGKAIL TVDKSSSTAY MELRSLTSED SAVYYCATYA MDYWGQGTSV TVSS), or hypervariable region thereof, and further wherein said antibody binds to human STRO-1 cell surface protein. 
     
     
         2 . The recombinant antibody of  claim 1 , wherein the hypervariable region of SEQ ID NO:1 is selected from the group of sequences comprising SEQ ID NO:3 (GYYMH), SEQ ID NO:4 (RVNPNNGGTSYNQKFK) and/or SEQ ID NO:5 (YCATYAMD). 
     
     
         3 . The antibody according to  claim 1 , wherein the antibody is immobilized on a solid support. 
     
     
         4 . The antibody according to  claim 1 , further comprising a detectable group conjugated thereto. 
     
     
         5 . The recombinant antibody of  claim 1 , wherein the antibody further comprises a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:2 (WNDVLCSLVD LCRACSSQAS VSTQTDYLTT SPGGTVILTC RCATGAVTTS NYANWVQEKP DHLFTGLIGG TSNRAPGVPV RFSGSLIGDK AALTITGAQT EDDAMYFSSL WYYGGHGVFG), or hypervariable region thereof. 
     
     
         6 . The recombinant antibody of  claim 5 , wherein the hypervariable region of SEQ ID NO:2 is selected from the group of sequences comprising SEQ ID NO:6 (QTDYLTTSPGG), SEQ ID NO:7 (SNYANWV) and/or SEQ ID NO:8 (DKAALTITG). 
     
     
         7 . The antibody according to  claim 5 , wherein the antibody is immobilized on a solid support. 
     
     
         8 . The antibody according to  claim 5 , further comprising a detectable group conjugated thereto. 
     
     
         9 . A method of isolating a cell in a cell sample, wherein the cell binds an antibody to human STRO-1 cell surface protein, said method comprising:
 contacting the cell sample with the antibody of  claim 1 , under conditions whereby the antibody can bind the cell; and   isolating the cell in the cell sample that binds to the antibody from the cells in the sample that do not bind to the antibody.   
     
     
         10 . The method of  claim 9 , wherein the antibody is immobilized in a solid support. 
     
     
         11 . The method of  claim 9 , wherein the antibody further comprises a detectable group conjugated thereto. 
     
     
         12 . A method of detecting a cell in a cell sample, wherein the cell comprises the human STRO-1 cell surface protein, said method comprising:
 contacting the cell sample with the antibody of  claim 1 , under conditions whereby an antibody can bind the cell; and   detecting the binding of the antibody to the cell in the sample, thereby detecting the cell comprising the human STRO-1 cell surface protein in the sample.   
     
     
         13 . The method of  claim 12 , wherein the antibody further comprises a detectable group conjugated thereto. 
     
     
         14 . The antibody of  claim 1 , further comprising a therapeutic agent conjugated thereto. 
     
     
         15 . The antibody of  claim 14 , wherein said therapeutic agent is selected from the group consisting of radionuclides, chemotherapeutic agents, and cytotoxic agents. 
     
     
         16 . The antibody of  claim 14 , wherein said antibody is conjugated to a radionuclide selected from the group consisting of  227 Ac,  211 At,  131 Ba,  77 Br,  109 Cd,  51 Cr,  67 Cu,  165 Dy,  155 Eu,  153 Gd,  198 Au,  166 Ho,  113m In,  115m In,  123 I,  125 I,  131 I,  189 Ir,  191 Ir,  192 Ir,  194 Ir,  52 Fe,  55 Fe,  59 Fe,  177 Lu,  109 Pd,  32 P,  226 Ra,  186 Re,  188 Re,  153 Sm,  46 Sc,  47 Sc,  72 Se,  75 Se,  105 Ag,  89 Sr,  35 S,  177 Ta,  117 mSn,  121 Sn,  166 Yb,  169 Yb,  90 Y,  212 Bi,  119 Sb,  197 Hg,  97 Ru,  100 Pd,  101m Rh, and  212 Pb. 
     
     
         17 . The antibody of  claim 14 , wherein said antibody is conjugated to a chemotherapeutic agent selected from the group consisting of methotrexate, daunomycin, mitomycin, cisplatin, vincristine, epirubicin, fluorouracil, verapamil, cyclophosphamide, cytosine arabinoside, aminopterin, bleomycin, mitomycin C, democolcine, etoposide, mithramycin, chlorambucil, melphalan, daunorubicin, doxorubicin, tamosifen, paclitaxel, vincristin, vinblastine, camptothecin, actinomycin D, and cytarabine 
     
     
         18 . The antibody of  claim 14 , wherein said antibody is conjugated to a cytotoxic agent selected from the group consisting of ricin, aclacinomycin, diphtheria toxin, Monensin, Verrucarin A, Abrin, Vinca alkaloids, Tricothecenes, and  Pseudomonas  exotoxin A. 
     
     
         19 . A method of inactivating a Stro-1 positive stem cell, comprising contacting a Stro-1 positive stem cell to an antibody of  claim 14 , said antibody provided in an amount effective to inactivate said Stro-1 positive stem cell. 
     
     
         20 . The method of  claim 19 , wherein said contacting step is carried out in vitro. 
     
     
         21 . The method of  claim 19 , wherein said contacting step is carried out in vivo.

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